Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy

Am J Hum Genet. 2010 Oct 8;87(4):538-44. doi: 10.1016/j.ajhg.2010.09.007.


The essential micronutrient selenium is found in proteins as selenocysteine (Sec), the only genetically encoded amino acid whose biosynthesis occurs on its cognate tRNA in humans. In the final step of selenocysteine formation, the essential enzyme SepSecS catalyzes the conversion of Sep-tRNA to Sec-tRNA. We demonstrate that SepSecS mutations cause autosomal-recessive progressive cerebellocerebral atrophy (PCCA) in Jews of Iraqi and Moroccan ancestry. Both founder mutations, common in these two populations, disrupt the sole route to the biosynthesis of the 21st amino acid, Sec, and thus to the generation of selenoproteins in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acyl-tRNA Synthetases / genetics*
  • Atrophy / genetics
  • Base Sequence
  • Cerebellum / pathology*
  • Cerebral Cortex / pathology*
  • Chromosome Mapping
  • Genes, Recessive
  • Heredodegenerative Disorders, Nervous System / genetics*
  • Heredodegenerative Disorders, Nervous System / pathology
  • Humans
  • Iraq / ethnology
  • Jews / genetics*
  • Molecular Sequence Data
  • Morocco / ethnology
  • Mutation / genetics
  • Pedigree
  • Selenocysteine / biosynthesis*
  • Sequence Alignment
  • Sequence Analysis, DNA


  • Selenocysteine
  • Amino Acyl-tRNA Synthetases
  • O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, human